3-Year Interim Safety Profile of Adeno-Associated Virus Serotype 2-soluble Variant of the Vascular Endothelial Growth Factor Receptor Type 1 (AAV2-sFLT01) Administered by Intravitreal Injection in Patients with Neovascular Age-Related Macular Degeneration

Abstract

Purpose : To characterize the 3-year preliminary safety profile of AAV2-sFLT01 administered by intravitreal injection (IVT) in patients with neovascular age-related macular degeneration participating in a Phase I trial

Methods : All reported treatment emergent adverse events (TEAEs) including descriptions, severity, relatedness to procedure or the investigational medicinal product (IMP) and event coding using MedDRA dictionary were collected and analyzed from an 52-week trial and through 2 years of a 4-year extended follow-up (EFU) program

Results : All patients treated with a single uniocular IVT completed the 52 weeks of the core trial. 17 of them elected to the EFU program and 12 completed the first 2 years of the extension. After 3 years, 18 (95%) patients experienced 136 TEAE, the most common being conjunctival hemorrhage, retinal hemorrhage, vitreous floaters and eye pain. The majority of TEAE were mild 85 (63%), occurred during the first year of FU and were related neither to the IVT procedure or IMP. 2 patients treated at highest dose experienced 6 TEAE related to IMP (vitritis, vitreous floaters, iritis and corneal deposits in one patient and pyrexia in the other). 9 patients experienced 13 TEAE related to the study procedure (conjunctival hemorrhage, edema, hyperemia, eyelid pruritus and eye pain). 7 patients reported 14 SAE, all non-ocular except for 3 retinal tears in the same patient. A death in a 91 year old patient could not be assessed by the investigator and thus was reported as a SAE attributed to the IMP and study procedure by the Sponsor. No AE that could be related to systemic exposure of the IMP or its transgene (sFLT01) were observed. A sustained reduction in retinal fluid was observed in 4 patients

Conclusions : A IVT administered gene providing sustained anti-VEGF expression may offer a convenient alternative to anti-VEGF treatments for wet AMD requiring repetitive injections and other gene therapies in development requiring delivery by subretinal injection following vitrectomy. After three years of follow up, AAV2-sFLT01 appears to be generally safe, well tolerated and does not appear to raise any new safety concerns relative to the established long-term safety profile of other intravitreally administered anti-VEGF therapies

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.